The studies were started last year and to date approximately 14 subjects were studied and two abstracts were submitted and presented (see abstract list, Erhard et al and Hickok et al). These performed in collaboration with Dr. Bellugi are based on their ongoing research on the biological foundations of human language approached through the study of American Sign Language (ASL). Dr. Peter Strick is also interested in ASL and native ASL speakers to investigate the role of Broca's area in language. Consequently, at the CMRR collaborative work related to ASL has commenced both with Dr. Bellugi's group and with Dr. Strick and paradigms generated by both groups have been recently examined with fMRI and native ASL speakers. ASL displays all of the complex linguistic structure of spoken languages, but encodes that information spatially. Thus, ASL allows one to dissociate modality dependent from modality independent contributions to the neural organization for language. ASL's extensive reliance on spatial contrasts in the encoding of linguistic structure would suggest a greater right hemisphere involvement; however, there is strong evidence from lesion studies that ASL is processed predominantly in the left cerebral hemisphere, and is to a large extent independent of non-linguistic spatial cognition. In addition, studies with ASL can allow the determination of whether Broca's area functions specifically in the realm of language or is a higher order motor field concerned with sequential movements. BOLD based functional Magnetic Resonance Imaging (fMRI) provides the opportunity to elucidate the neural substrate of ASL and the cortical representation of language in general. This approach was employed to map activated regions in deaf subjects who are native ASL users during covert and overt signing and during a motor control task that involved reproducing "nonsense" hand shapes. MRI experiments were performed using twenty eight contiguous, multislice BOLD based fMRI images (TE = 20 ms; 50 ms/each image; 64x64; FOV = 20x20 cm2; slice thickness 5 mm) acquired with blipped EPI. Four tasks were examined: (a) covert signing of objects: subjects were asked to imagine the ASL signs for objects displayed on the screen in succession every 2 second (bee, flower, apple, car etc.; objects that would be spelled using the English-based manual alphabet rather than represented were avoided); (b) overt signing of objects with one hand: same as the covert task but subjects produced the signs with the hand adjacent to their leg to minimize motion (this is not an unnatural task and this form of signing is employed in situations requiring some degree of privacy; it is commonly referred to as "whispering"); (c) covert sign generation: subjects were shown a hand shape every 5 seconds and were asked to think of as many ASL signs as they could that contained that handshape; (d) reproducing "nonsense" hand-shapes; subjects were asked to reproduce nonsense hand shapes displayed to them in succession on the back projection screen. During the paradigms, task periods were alternated with "baseline" periods during which the subjects were shown a flickering "noise" pattern on the screen. The activation maps were generated by a t-test screening for task-related changes relative to this baseline. A total of 7 deaf native signers were examined. The data presented below are from 2 subjects analyzed so far for covert signing and motor control paradigms, and 1 subject analyzed for overt signing at the present time, and represent preliminary results. Extensive and consistent activation was observed during the aforelisted paradigms. Most notably, in both covert tasks, areas activated included i) areas dorsal to the sylvian fissure including area 44 (Broca's area), ii) portions of areas 9 and 8, iii) medial wall motor areas (including potions of supplementary motor area (SMA), preSMA, and the cingulate motor areas buried in the cingulate sulcus) iv) lateral motor areas 4 and 6 (despite no actual signing) v) area 7, 40, 42, and 22 of the parietal cortex; vi) a portion of area 24 located anteriorly in the cingulate gyrus. Activation in the medial wall motor areas, anterior cingulate gyrus and prefrontal cortex were not as extensive in the motor control paradigm (reproduction of nonsense hand shapes). Of special note, regions of Broca's area that were activated during covert signing were also activated during the performance non-representational hand-movements. This observation suggests either of two exciting possibilities: i) Broca's areas is not exclusively related to language function as generally assumed but may represent a higher order premotor area related to sequencing of motor acts or ii) significant plasticity of brain function has occurred in deaf subjects who are native ASL users. These possibilities are currently being explored in additional experiments which include imaging hearing subjects who are native English speakers.